Nearly two-thirds of the US population is either clinically overweight or obese and almost 10% of the population has adult-onset diabetes. Obesity and diabetes are central elements of a cluster of pathologies collectively referred to as metabolic syndrome. Our Center of Biomedical Research Excellence (COBRE) at the Pennington Biomedical Research Center is leading an effort to enhance research on metabolic disease by mentoring our most promising young scientists to independence by senior scientists within the Center. The scope of work undertaken by COBRE scientists encompasses a combination of cellular, molecular, and translational approaches to address questions ranging from neural mechanisms of glucose sensing and energy homeostasis, inflammatory mechanisms linked to adipogenesis, epigenetic programming in obesity, regulation of mitochondrial biogenesis in adipocytes, and the role of inflammation in pancreatic beta cell function. Our COBRE has developed the scientific infrastructure to support the pursuit of these diverse objectives by establishing state of the art Genomics, Cell Biology and Bioimaging, and Transgenic Cores. The Specific Aims of our COBRE in Phase III are to further expand the critical mass of productive investigators engaged in obesity/diabetes research by (a) develop and retain outstanding new junior faculty from within the institution and mentor them to sustainable independent funding (b) recruit outstanding junior and senior faculty engaged in metabolic disease research that complement existing strengths of Center investigators; (c) develop and foster new opportunities for collaborative interactions with institutional colleagues by instituting a new Pilot and Feasibility funding program, (d) enhance utilization of the outstanding research infrastructure developed within the Cell Biology and Bioimaging, Genomics, and Transgenic core facilities in Phase III through development of training modules and outreach activites. The critical metrics of success are to expand the number of extramural grants obtained by the COBRE faculty, increase the number of faculty engaged in metabolic diseases research, leverage COBRE support to expand the quality of our scientific cores through increased utilization and investment of institutional resources.